Most of the expiratory neurones located in the caudal part of the ventral respiratory group (cVRG) are bulbospinal neurones (Bianchi et al. 1995). Although several lines of evidence indicate that the cVRG is not essential for respiratory rhythm generation, chemical activation of this structure via microinjections of the broad-spectrum excitatory amino acid (EAA) agonist, DL-homocysteic acid, suggests that cVRG expiratory neurones have ionotropic EAA receptors and may affect the pattern of breathing when strongly activated (Bongianni et al. 1994). This could be relevant to some physiological conditions, such as cough and other reflexes characterized by the activation of expiratory muscles. Cough probably involves the same neuronal network as subserves respiratory rhythm generation (Bongianni et al. 1998; Shannon et al. 2000). The aim of the present study was to investigate the functional role of ionotropic glutamate receptors in the excitatory drive transmission to cVRG expiratory neurones during eupnoeic breathing as well as during cough induced by mechanical stimulation of the tracheobronchial tree and other respiratory reflexes.
All experimental procedures were conducted in accordance with Italian legislation. Microinjections (30Ð50 nl) of antagonists acting on either NMDA or non-NMDA receptors were made into the cVRG of spontaneously breathing rabbits (n = 18) under pentobarbitone anaesthesia (40 mg kg-1, I.V., supplemented by 3Ð5 mg kg-1 every 30 min). Phrenic nerve and abdominal muscle activities were recorded. Blockade of both NMDA and non-NMDA receptors by kynurenic acid (KYN; 50 mM) suppressed spontaneous rhythmic activity of abdominal muscles and the inspiratory and expiratory components of the cough reflex. Microinjections of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 mM) caused similar results. Microinjections of the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 10 mM) strongly reduced, but did not abolish spontaneous abdominal activity and the cough reflex. The activation of abdominal muscles induced either by tracheal occlusion at end-inspiration or by expiratory threshold loads (5 cmH2O) was completely abolished by KYN and CNQX and strongly reduced by D-AP5.
The results indicate that the excitatory drive to cVRG expiratory neurones is mediated by ionotropic glutamate receptors during eupnoeic breathing, coughing, inflation reflex and expiratory threshold loading; non-NMDA receptors appear to play a major role. In addition, cVRG expiratory neurones appear to be of crucial importance in determining not only the expiratory, but also the inspiratory component of the cough motor pattern, thus supporting the view that these neurones are not merely upper motoneurones conveying the expiratory drive to the spinal cord (Bongianni et al. 1994).
This study was supported by grants from the Ministero dell’Istruzione, Universitˆ e Ricerca of Italy.
All procedures accord with current national legislation.